UNITED STATES PATENT AND TRADEMARK OFFICE
`_______________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`_____________
`
`ARGENTUM PHARMACEUTICALS LLC
`Petitioner
`
`v.
`
`ALCON RESEARCH, LTD.
`Patent Owner
`
`
`Patent No. 8,268,299
`Issue Date: September 18, 2012
`Title: SELF PRESERVED AQUEOUS PHARMACEUTICAL COMPOSITIONS
`
`
`
`Inter Partes Review No. IPR2017-01053
`
`
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`PETITIONER’S RESPONSE TO ALCON RESEARCH, LTD.’S MOTION
`FOR OBSERVATIONS ON THE DEPOSITION OF PETITIONER’S
`EXPERT DR. YVONNE M. BUYS, M.D.
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`_______________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`_____________
`
`ARGENTUM PHARMACEUTICALS LLC
`Petitioner
`
`v.
`
`ALCON RESEARCH, LTD.
`Patent Owner
`
`
`Patent No. 8,268,299
`Issue Date: September 18, 2012
`Title: SELF PRESERVED AQUEOUS PHARMACEUTICAL COMPOSITIONS
`
`
`
`Inter Partes Review No. IPR2017-01053
`
`
`
`PETITIONER’S RESPONSE TO ALCON RESEARCH, LTD.’S MOTION
`FOR OBSERVATIONS ON THE DEPOSITION OF PETITIONER’S
`EXPERT DR. YVONNE M. BUYS, M.D.
`
`
`
`
`
`
`
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`Petitioner Argentum Pharmaceuticals LLC (“Petitioner”) hereby responds to
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`Alcon Research Ltd.’s motion for observations on the deposition of Petitioner’s
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`expert Dr. Yvonne M. Buys, M.D. (Paper 44, hereafter “Mot.”). Office Patent
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`Trial Practice Guide, 77 Fed. Reg. 48756 at 48767-68 (August 14, 2012).
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`Observation #1: Patent Owner’s assertion that Dr. Buy’s cited testimony
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`undermines the premise of Petitioner’s argument that surgery or laser treatments
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`are suitable or equivalent options to medical therapy overlooks Dr. Buys’ other
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`relevant testimony. Dr. Buys pointed out statements in Exhibit 2129 teaching that
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`laser treatments “can be considered as initial therapy in selected patients or an
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`alternative for patients at high risk for nonadherence to medical therapy who
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`cannot or will not use medications reliably due to cost, memory problems,
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`difficulty with installation or intolerance to the medication.” See EX2167, 11:6-
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`12:9. Dr. Buys further testified that several large trials done prior to 2006
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`supported using laser treatments as the initial therapy because it can be superior to
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`medical treatment in preserving visual fields and optic nerve status, and also in
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`achieving lower intraocular pressures. Id., 13:7-13. Dr. Buys also testified that
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`surgical and laser treatments achieve the dual goals of both lowering IOP and
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`avoiding the exacerbation of OSD symptoms, and that surgical treatment options
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`would not typically be expected to cause or exacerbate OSD symptoms because
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`
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`1
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`
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`successful procedures do not require ongoing medical management. EX1092,
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`¶11.1
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`Observation #2: Patent Owner’s assertion that Dr. Buy’s cited testimony
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`undermines the premise of Petitioner’s argument that single-use containers are just
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`as desirable as multi-use containers both misapprehends Petitioner’s argument and
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`overlooks other relevant testimony. Both Dr. Buys and Patent Owner’s expert, Dr.
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`Majumdar, agree that any given PGA drug could easily have been formulated as
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`preservative-free simply by packaging it in single-dose form. EX1092, ¶¶15, 17;
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`EX2023, ¶45; EX1045, 107:12-108:9. Dr. Buys further testified that the only
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`possible advantage of multi-use packaging versus single-use packaging was “ease
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`of use.” EX2167, 22:21-23. This testimony supports Petitioner’s argument that
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`any alleged “need” identified by Patent Owner was nonexistent or at most, quite
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`modest. Paper 35 at 26.
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`Observation #3: Patent Owner’s assertion that Dr. Buys’ cited testimony
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`contradicts Petitioner’s argument is false. First, Petitioner pointed out that many of
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`the claims at issue do not require a therapeutic agent at all (compare claims 1 and
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`1 Dr. Buys pointed out that a mis-citation occurred in paragraphs 11 and 12 of her
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`reply declaration, such that the cite to “ALCON2011, pp. 24-27” in paragraph 11
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`should be “Exhibit 2129, P70-P75,” and the citation to “ALCON2011, pp. 22-23”
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`should be to “Exhibit 2129, P68-P69.” See EX2167, 59:5-61:17.
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`2
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`4), let alone an agent for glaucoma (compare claims 1 and 6). Paper 35 at 25.
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`Second, both Dr. Buys and Patent Owner’s expert, Dr. Majumdar, agree that any
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`given PGA drug could easily have been formulated as preservative-free simply by
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`packaging it in single-dose form, thereby meeting any need for a drug-treatment
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`option not containing a traditional preservative. EX1092, ¶¶15, 17; EX2023, ¶45;
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`EX1045, 107:12-108:9. Lastly, Dr. Buys testified that because Travatan Z has
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`never been shown to reduce OSD symptoms and may in fact exacerbate such
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`symptoms (see EX1092, ¶¶20-39), her current practice is to prescribe Monoprost,
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`which contains the PGA drug latanoprost packaged in single-dose form such that
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`no preservatives are present. EX2167, 35:23-36:14; EX1092, ¶16. This testimony
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`does not contradict but instead supports Petitioner’s argument that there was no
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`unmet need for a preservative-free PGA treatment, and to the extent any such need
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`did exist, Travatan Z did not meet it. EX1092, ¶¶18-19, 20-39; Paper 35 at 26-27.
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`Observation #4: Patent Owner’s assertion that Dr. Buys’ cited testimony
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`contradicts Petitioner’s argument is false. Regarding Exhibit 2132, Dr. Buys
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`testified in her deposition that:
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`Answer: I am not sure if we mentioned that specific result, but
`that -- what I was quoting in the declaration was the main
`purpose of this study was to look at the average OSDI scores
`for the entire population, and then they did several subanalyses;
`and I think there's close to 20 comparisons in this paper, of
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`
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`3
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`
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`which only 2 were favorable to show that BAK was -- to show
`that not using BAK or not having BAK in the medication was
`associated with a better result, whereas the majority of
`outcomes studied in this paper did not find any difference
`between Travatan, travoprost with or without BAK…. This is a
`swing, like they're kind of swinging the results to try to pull out
`the ones that had a positive response and ignoring the majority
`of them that did not show an effect.
`
`****
`
`[T]he main outcome measure did not have a significant result;
`and the numerous other comparisons, for example just looking
`at mean change in the overall group and those with moderate
`and severe OSDI symptoms, did not show a significant
`difference between the groups.
`
`****
`
`My point was to find that the paper was misleading as it is
`because it has so many results that did not show an effect, mind
`you the abstract conclusions tried to suggest that it was
`beneficial, where I don't think you can conclude this when you
`actually critically look at the paper.
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`****
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`[The Discussion section] highlights those and fails to highlight
`the nonsignificant results, which is not surprising at all in a
`paper that was not only funded by a drug company but actually
`also they funded the writer of the paper, which is written in the
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`4
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`disclosure that this study was funded by Alcon Research
`Limited which also provided the assistance of a medical writer;
`and that is hugely problematic because they are not fairly
`presenting the results of this study.
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`****
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`[T]he results that were significant were only those in mild
`disease who you would not change. You're looking to change it
`in people who have moderate or severe OSD symptoms, and
`there was no significant improvement in that cohort of patients;
`and those are the ones that you're really looking for this unmet
`need.
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`EX2167, 26:16-34:9. Dr. Buys’ testimony supports rather than contradicts
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`Petitioner’s argument that the data presented in Exhibit 2132 does not support the
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`paper’s conclusory statements about the alleged benefits of Travatan Z.
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`Observation #5: Patent Owner’s assertion that Dr. Buys’ cited testimony
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`contradicts Petitioner’s argument and undermines Dr. Buys’ credibility is false. At
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`paragraph 37 of her reply declaration, Dr. Buys recited the data from Table 2 of
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`Exhibit 2132, showing that 30 adverse ocular events occurred in patients taking
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`Travatan Z, while the latanoprost formulation containing BAK resulted in only 18
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`adverse events. In her declaration, Dr. Buys explained the relevance of an express
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`finding that a numerical difference is not statistically significant (EX1092, ¶24
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`n.2)—however, Exhibit 2132 contains no such express finding as to whether the
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`5
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`difference in adverse events reported in Table 2 is statistically significant
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`(EX2167, 38:7-11), and Dr. Buys nowhere claimed otherwise. The cited
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`deposition testimony is therefore consistent with Dr. Buys’ declaration testimony
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`and Petitioner’s arguments based thereon.
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`Observation #6: Patent Owner’s assertion that Dr. Buys’ cited testimony
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`undermines her credibility is incorrect. Dr. Buys explained in her declaration that
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`the study reported in Exhibit 1091 was particularly reliable because it was a
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`randomized and investigator masked study, and the study’s conclusions were based
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`on objective clinical measures of ocular tolerability, including physician-graded
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`hyperemia, corneal staining, and tear breakup time. EX1092, ¶¶34-35. Dr. Buys
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`also explained that she did not discuss the author affiliations for any of the studies
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`discussed in her declaration. EX2167, 51:19-23. Nonetheless, Dr. Buys pointed
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`out that the majority of the authors (3 out of 5) of the study reported in Exhibit
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`1091 had affiliations with Alcon. Id., 57:9-58:11. This testimony supports Dr.
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`Buys’ conclusion that the study in Exhibit 1091 was particularly reliable.
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`Dated: May 25, 2018
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`Respectfully submitted,
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`
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`By: /Michael R. Houston/
`
`Michael Houston
`Registration No. 58,486
`FOLEY & LARDNER LLP
`321 North Clark Street, Suite 2800
`Chicago, Illinois 60654
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`6
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`Telephone: 312-832-4500
`Facsimile: 312-832-4700
`mhouston@foley.com
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`Counsel for Petitioner
`Argentum Pharmaceuticals LLC
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`7
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`CERTIFICATION OF SERVICE
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`The undersigned hereby certifies that a copy of the foregoing
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`PETITIONER’S RESPONSE TO ALCON RESEARCH, LTD.’S MOTION
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`FOR OBSERVATIONS ON THE DEPOSITION OF PETITIONER’S
`
`EXPERT DR. YVONNE M. BUYS, M.D. was served on May 25, 2018, on
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`Counsel for Patent Owner via electronic mail to the following:
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`Dated: May 25, 2018
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`dkrinsky@wc.com
`csuarez@wc.com
`TravZ-IPR@wc.com
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`By: /Michael R. Houston/
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`Michael Houston
`Registration No. 58,486
`Counsel for Petitioner
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